Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of
neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in
neurodegenerative diseases, so the present study aimed to observe the effects of
ginsenoside Rb1 on ER stress signaling pathways in high
glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and
Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high
glucose for 72 h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72 h protected the neurons against high
glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated
proteins including
protein kinase RNA (PKR)-like ER
kinase (PERK) and C/EBP homology
protein (CHOP) and downregulation of Bcl-2 induced by high
glucose. Moreover, Rb1 inhibited both the elevation of intracellular
reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high
glucose. In addition, the high
glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and
mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress
4-phenylbutyric acid (4-PBA) and
anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high
glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and
mitochondrial dysfunction.